All-Trans Retinoic Acid Enhances Antibody Production by Inducing the Expression of Thymic Stromal Lymphopoietin Protein.

Many classical vaccines contain whole pathogens and, thus, may occasionally induce adverse effects, such as inflammation. Vaccines containing purified rAgs resolved this problem, but, owing to their low antigenicity, they require adjuvants. Recently, the use of several cytokines, including thymic stromal lymphopoietin (TSLP), has been proposed for this purpose. However, it is difficult to use cytokines as vaccine adjuvants in clinical practice. In this study, we examined the effects of all-trans retinoic acid (atRA) on TSLP production and Ag-induced Ab production. Application of atRA onto the ear lobes of mice selectively induced TSLP production without inducing apparent inflammation. The effects appeared to be regulated via retinoic acid receptors γ and α. Treatment with atRA was observed to enhance OVA-induced specific Ab production; however, this effect was completely absent in TSLP receptor-knockout mice. An enhancement in Ab production was also observed when recombinant hemagglutinin was used as the Ag. In conclusion, atRA was an effective adjuvant through induction of TSLP production. Therefore, we propose that TSLP-inducing low m.w. compounds, such as atRA, may serve as effective adjuvants for next-generation vaccines.

Cerebral blood flow velocity before and after cerebrospinal fluid drainage in infants with posthemorrhagic hydrocephalus.

OBJECTIVE: Currently, the timing and volume of cerebrospinal fluid (CSF) drainage are determined by subjective clinical findings in infants with posthemorrhagic hydrocephalus. The aim of this study was to determine whether measurement of the resistive index is useful for management of CSF drainage in these infants. METHODS: We measured the resistive index in the anterior cerebral artery (RI-ACA) by using pulsed Doppler sonography before and after lumbar or subcutaneous ventricular catheter reservoir punctures in 7 infants with posthemorrhagic hydrocephalus. RESULTS: The increased RI-ACA values (mean +/- SD, 0.86 +/- 0.04; range, 0.80-0.89) decreased significantly (0.76 +/- 0.05; 0.64-0.83) after removal of CSF at a rate of 5 to 10 mL/kg (P <.0001). CONCLUSIONS: We suggest that measurement of the RI-ACA may be useful for evaluating the efficacy of CSF drainage and to determine how much CSF should be removed in hydrocephalic infants.

Effects of phototherapy in neonates on circadian sleep-wake and saliva cortisol level rhythms.

The influence of phototherapy treatment during the neonatal period on sleep-wake rhythm, and its long-term effects on biological rhythms, was evaluated in preterm and full-term infants. Forty-three infants treated with phototherapy during the neonatal period and 47 untreated infants were examined for entrainment of sleep-wake rhythms between 16 and 52 weeks and for sleep-wake and saliva cortisol rhythms at 2.5 years of age. The age of sleep-wake rhythm entrainment was not significantly different between the 2 groups. No correlations between duration of exposure to phototherapy and corrected age of entrainment of sleep-wake rhythm were observed. At follow-up, no significant differences in sleep-wake and saliva cortisol rhythms were observed between the 2 groups, indicating that circadian variations were similar to those in adults.

Inhibitors of adhesion molecules expression; the synthesis and pharmacological properties of 10H-pyrazino[2,3-b][1,4]benzothiazine derivatives.

During a search for novel, orally-active inhibitors of upregulation of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), we found a new series of 10H-pyrazino[2,3-b][1,4]benzothiazine derivatives to be potent ICAM-1 inhibitors. Of these compounds, N-[1-(10H-Pyrazino[2,3-b][1,4]benzothiazin-8-ylmethyl)piperidin-4-yl]-N',N'-dimethylsulfamide 7p showed the potent oral inhibitory activities against neutrophil migration in a murine interleukin-1 (IL-1) induced paw inflammation model. The synthesis and structure-activity relationships of these amide derivatives are described.